[P2-95] Hypercapnia-induced brain acidosis: effects and putative mechanisms on acute kainate induced seizures
The anticonvulsant effect of CO2 was previously demonstrated, although its mechanisms remain unclear. This study investigated the mechanism of the anticonvulsant effects of carbogen containing 5% CO2 in a kainic acid (KA) rat model. Four-week-old Sprague–Dawley rats were divided into four groups: control, carbogen, KA+air, and KA+carbogen. Carbogen was applied immediately after KA injection, and cortical pH was recorded. High-performance liquid chromatography was used to detect the release of γ-aminobutyric acid (GABA) and glutamate. We used electrophysiology to measure cortical and hippocampal activities. Carbogen increased the onset latency of seizure (KA+air group, 26.12 ± 2.11 min; KA+carbogen group 43.65 ± 2.78 min, P < 0.001) and reduced the frequency of seizures (KA+air group, 12.50 ± 1.77; KA+carbogen group, 5.63 ± 1.59, P < 0.001). Carbogen inhalation could reduce cortical pH (KA+air group, 7.04 ± 0.04; KA+carbogen group, 6.82 ± 0.03, P < 0.001). After carbogen inhalation, the levels of excitatory amino acid glutamate decreased (595.90 ± 7.51 in KA+air group vs. 467.95 ± 4.82 in KA+carbogen s group, P < 0.001), whereas GABA increased significantly (158.30 ± 5.05 in KA+air group vs. 216.62 ± 5.59 in KA+carbogen, P < 0.05). Carbogen reduced both electrohippocampalogram (119.57 ± 2.83 in KA+air group vs. 107.48 ± 2.95 in KA+carbogen group, P < 0.01) and electrocorticogram (130.74 ± 2.48 in KA+air group vs. 115.35 ± 2.11 in KA+carbogen group, P < 0.01). These findings demonstrate that carbogen suppressed seizures by reducing cortical pH, by increasing GAGA release, and by affecting electrical activity of the brain.